Biomedical subjects

Guillaume Belliard

Publications and source records attributed to Guillaume Belliard.

6 recordsLinked to original sources

PubMed2006

Genes required for osmoregulation and apical secretion in Caenorhabditis elegans.

Few studies have investigated whether or not there is an interdependence between osmoregulation and vesicular trafficking. We previously showed that in Caenorhabditis elegans che-14 mutations affect osmoregulation, cuticle secretion, and sensory organ development. We report the identification of seven lethal mutations displaying che-14-like phenotypes, which define four new genes, rdy-1-rdy-4 (rod-like larval lethality and dye-filling defective). rdy-1, rdy-2, and rdy-4 mutations affect excretory canal function and cuticle formation. Moreover, rdy-1 and rdy-2 mutations reduce the amount of matrix material normally secreted by sheath cells in the amphid channel. In contrast, rdy-3 mutants have short cystic excretory canals, suggesting that it acts in a different process. rdy-1 encodes the vacuolar H+-ATPase a-subunit VHA-5, whereas rdy-2 encodes a new tetraspan protein. We suggest that RDY-1/VHA-5 acts upstream of RDY-2 and CHE-14 in some tissues, since it is required for their delivery to the epidermal, but not the amphid sheath, apical plasma membrane. Hence, the RDY-1/VHA-5 trafficking function appears essential in some cells and its proton pump function essential in others. Finally, we show that RDY-1/VHA-5 distribution changes prior to molting in parallel with that of actin microfilaments and propose a model for molting whereby actin provides a spatial cue for secretion.

Actin Cytoskeleton↗

PubMed2006

[Circulatory failures].

To treat circulatory failures and recognize their mechanisms, we need to understand circulatory physiology. What determines systemic venous return? How does the right ventricle feed the pulmonary circulation? Where is the left ventricular preload reserve located? Four types of circulatory failure are conventionally recognized: hypovolemic, obstructive, vasoplegic and cardiogenic. One or more of these mechanisms may account for circulatory failure in septic shock. Treatment of circulatory failure requires admission to a specialized unit and continuous or discontinuous hemodynamic monitoring. Prognosis is highly dependent on rapid treatment and correction of circulatory impairment.

Algorithms↗

PubMed2005

[Fluvastatin affects HLA class I expression on endothelial cells].

Originally designed to target elevated lipids, the "traditional" cause of atherosclerosis, statins might also confer vascular benefit by directly or indirectly modulating both the inflammatory and immune responses. Statins have been shown to downregulate MHC class II and CD40 expression on activated endothelial cells (EC). In this study, we investigate the potential effect of statins on MHC class I expression and regulation in response to IFNgamma. Primary cultures of human ECs have been treated with increasing doses of fluvastatin (0.01; 0.1 and 1 microM) with or without IFNgamma for 48 hours. Surface expression of MHC class I and class II has been analyzed by flow cytometry. Our data indicate that fluvastatin increases MHC class I expression on quiescent ECs by a dose-dependent effect. Furthermore, fluvastatin potentiates the MHC class I upregulation but prevents MHC class II induction triggered by IFNgamma. These effects are reversed by mevalonate. In conclusion, our results suggest that while decreasing MHC class II expression, fluvastatin (at 0.1 and 1 microM) upregulates MHC class I expression on ECs. Functional consequences of statin-mediated modulation of MHC on ECs have still to be elucidated in vitro and in vivo.

Cells, Cultured↗

PubMed2005

Tat-neutralizing versus Tat-protecting antibodies in rhesus macaques vaccinated with Tat peptides.

The human immunodeficiency virus (HIV) regulatory protein Tat represents an attractive target for developing vaccine strategies. Both humoral and cellular responses against Tat might reduce disease progression by interfering with the deleterious functions of extracellularly secreted protein and by reducing viral replication. We have immunized Rhesus macaques intramuscularly and intranasally with a cocktail of three Tat peptides encompassing residues 1-20, 1-61 and 44-61 administrated in the presence of Montanide ISA 720 as adjuvant. The monkeys were challenged by the intrarectal route with 10 MID50 of SHIV BX08. All immunized macaques but one gave a good cross-reactive antibody response to Tat but the proliferative response and levels of IL-2, IFN-gamma and TNF-alpha secretion of peripheral blood mononuclear cells (PBMCs) recalled ex vivo with active Tat protein were weak. After viral challenge one peptide-vaccinated macaque only remained free of virus. The presence in the serum of vaccinated animals of neutralizing antibodies able to inhibit Tat transactivation activity or Tat-induced apoptosis was not correlated to protection.

AIDS Vaccines↗

PubMed2005

The binding affinity of double-stranded RNA motifs to HIV-1 Tat protein affects transactivation and the neutralizing capacity of anti-Tat antibodies elicited after intranasal immunization.

In this study we examined the hypothesis that the binding affinity of two double-stranded (ds) RNA motifs to HIV-1 Tat protein might affect transactivation and the type of anti-Tat immune responses. Using surface plasmon resonance technology we demonstrated the capacity of the poly(A):poly(U) (pA:pU) motif to bind with high affinity to a totally synthetic Tat protein and to inhibit more efficiently the Tat/transactivation response element (TAR) RNA interaction as compared to the poly(I):poly(C) (pI:pC) motif. Furthermore, the pA:pU motif was tenfold more effective in inhibiting Tat-driven transactivation than the pI:pC motif. Following intranasal immunization of mice, both dsRNA motifs enhanced the antibody (serum and mucosal) and cellular responses to Tat. However, only the serum samples of mice immunized with Tat + pI:pC inhibited Tat-driven transactivation. The profile of serum antibody subclasses together with the secreted cytokines by Tat-stimulated splenocyte cultures indicated that both dsRNA motifs favored the induction of a balanced Th1 and Th2 immune response. The demonstration in this study that two dsRNA motifs had a marked effect on Tat/TAR RNA interaction and on the neutralizing capacity of anti-Tat specific antibody responses highlights their potential for biological applications and the importance of selecting the appropriate motif as an adjuvant for vaccine design.

Administration, Intranasal↗

PubMed2003

Specificity and effect on apoptosis of Tat antibodies from vaccinated and SHIV-infected rhesus macaques and HIV-infected individuals.

Recent contributions have demonstrated that actively secreted Tat protein plays an important functional role in human immunodeficiency virus-1 (HIV-1) infection and that Tat antibodies might interfere with disease progression by blocking the protein extracellularly. In this context we have studied the recognition of several Tat mutants as well as various synthetic Tat fragments by anti-Tat monoclonal antibodies and by IgG antibodies from a large collection of slow and fast-progressor infected individuals. We have also tested the sera from simian/human immunodeficiency virus (SHIV)-infected macaques with these Tat peptides. Important differences were found between long-term non-progressors and fast-progressors, and between human and monkey sera in terms of antibody specificity. Rabbits and macaques were immunised with several Tat peptides and we found that certain antibody subsets from immunised animals recognised the cognate protein Tat and had the capacity to inhibit Tat-induced apoptosis of T cells. Such antibodies might be important for controlling Tat-induced death in cells uninfected by HIV-1.

Amino Acid Sequence↗